Sucralose (4,1′,6′-trichloro-4,1′,6′-trideoxy-galactosucrose, or 1,6-dichloro -1,6-dideoxy-β-D-fructofuranosyl-4-chloro-4-deoxy-α-D-galactopyranoside) is an artificial sweetener derived from sucrose. It is about 600 times sweeter than cane sugar. It is considered safe because it is excreted in humans without undergoing any metabolism. It has high resistance to acid hydrolysis and is highly stable to heat. Because of these advantages, sucralose is one of the most widely used sweeteners in the market.
Synthesis of sucralose involves substitution of two primary alcohol groups at the 1′ and 6′ positions and a secondary alcohol group at the 4 position with chlorine. During the chlorination (for the sake of simplicity this reaction will be referred henceforth as ‘chlorination’) the other primary alcohol group at the 6-position should not be affected. This is generally achieved by selective esterification of a primary alcohol at the 6 position before chlorination. Finally the ester is hydrolyzed to obtain sucralose.
The Tate & Lyle group has developed a method for the preparation of sucrose-6-acetate selectively through an ortho ester intermediate (U.S. Pat. No. 4,889,928).
Chlorination of sucrose-6-acetate is a typical SN2 substitution reaction resulting in inversion of the configuration at the 4-position. Because of this inversion, the glucose ring gets converted to a galactose ring. Thus, trichlorination of sucrose-6-acetate gives 4,1′,6′-trichloro-4,1′,6′-trideoxy-galactosucrose-6-acetate (TGS-6-acetate) In most cases, a Vilsmeier type reagent is preferred for the trichlorination of sucrose-6-acetate (U.S. Pat. Nos. 4,380,476; 4,617,269; and 4,980,463). U.S. Pat. No. 4,980,463 describes the use of a Vilsmeier reagent prepared from phosgene and dimethylformamide (DMF) for the chlorination of sucrose-6-acetate. Triphosgene, which is a safer alternative to phosgene, has been used for the preparation of a Vilsemeier reagent from DMF. (US 2008/0103298 A1). Chlorination of sucrose-6-ester with a Vilsmeier reagent is a complex reaction. For the chlorination at all three positions, a temperature of about 100-120° C. is required and the reaction is to be maintained at this temperature for several hours. The severe conditions required for complete chlorination results in a dark brown to black reaction mass. Irrespective of the workup methods, the TGS-6-acetate is always obtained as a highly colored product. Almost all reported methods describe the use of activated charcoal for the decolorization (US 2007/0207246A1; US 2008/0300401 A1; US 2008/0103298A1). US application US 2007/0207246A1 describes a process where TGS-6-acetate was decolorized using activated charcoal and after ester hydrolysis, the final sucralose product needed to be again decolorized using charcoal. The application US 2008/0300401A1 describes a process where TGS-6-acetate was decolorized twice using activated charcoal and after ester hydrolysis, the final sucralose product was again decolorized using charcoal for a third time.
TGS-6-acetate is hydrolyzed to sucralose using a base such as sodium methoxide (U.S. Pat. No. 4,380,476, US 2009/0227783), sodium hydroxide (U.S. Pat. No. 5,498,709), potassium hydroxide (US 2007/0207246) or an organic base such as triethylamine (U.S. Pat. No. 7,838,642). When sodium methoxide is used, the conversion remains incomplete. Hydrolysis using organic base is also slow and the acetate salts of the organic bases formed in the reaction have similar solubility as sucralose and their removal is difficult.
Thus, there is a strong need for an efficient process to decolorize TGS-6-acetate and sucralose. There is also a need for a rapid method for the hydrolysis of TGS-6-acetate to obtain sucralose.